Structure and antibiotic activity of a porcine myeloid antibacterial peptide, PMAP-23 and its analogues

Abstract

PMAP-23 is a 23-residue antimicrobial peptide derived from porcine myloid cells. In order to investigate the effects of two Pro residues at positions 12 and 15 of PMAP-23 on antibiotic activity, two analogues in which Ala was substituted for Pro residue at position 12 or 15 were synthesized. Pro12→Ala (PMAP1) or Pro15→Ala (PMAP2) substitution in PMAP-23 caused a significant reduction on antitumor and phospholipid vesicle-disrupting activities, but did not cause a significant effect on antibacterial activity. PMAP-23 displayed the type I β-turn structure with a negative ellipticity at near 205 nm in SDS micelle, whereas PMAP1 and PMAP2 had a somewhat α-helical propensity in TFE solution, as compared to PMAP-23. These results suggest that two Pro residues of positions 12 and 15 in PMAP-23 play important roles in the formation of β-turn structure on lipid membrane and its β-turn structure may be essential for antibiotic activity including phospholipid vesicle-disrupting property.